title: Effects of the neurotrophic agent T-817MA on oligomeric amyloid-β-induced deficits in long-term potentiation in the hippocampal CA1 subfield.
abstract: Formation of oligomeric amyloid-β (oAβ) is 1 of the most likely causes of Alzheimer's disease (AD). We hypothesized that in the early phase of AD, cognitive impairments observed before marked neuronal loss and brain atrophy might be associated with oAβ-induced synaptic dysfunction. T-817MA [1-{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl}azetidin-3-ol maleate] has both neuroprotective and neurotrophic effects and is used to treat AD. Although T-817MA has been shown to ameliorate amyloid-induced learning deficits in experimental AD models, it remains unclear whether this drug would be able to prevent oAβ-induced synaptotoxicity. In the present study, we investigated the effects of T-817MA on the disturbances in synaptic plasticity induced by oAβ42 and oligomeric photo-cross-linked Aβ42 (oXLAβ42) in a slice preparation of the CA1 subfield of mouse hippocampus. Both oAβ42 and oXLAβ42 treatments significantly reduced the induction of long-term potentiation (LTP). In addition, oAβ42 treatment significantly facilitated long-term depression (LTD). Treatment with T-817MA ameliorated the LTP reduction; however, T-817MA treatment did not inhibit the facilitation of LTD induction by oAβ42. These results suggest that T-817MA reverses oAβ-induced LTP reduction as it may occur in the early phase of AD.
authors.affiliation: System Emotional Science, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Toyama, Japan.
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Takamura
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Ono
authors.forename: Jumpei
authors.initials: J
authors.lastname: Matsumoto
authors.forename: Masahito
authors.initials: M
authors.lastname: Yamada
authors.forename: Hisao
authors.initials: H
authors.lastname: Nishijo
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001284:Atrophy; D056547:CA1 Region, Hippocampal / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D008298:Maleates / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D013569:Synapses / Q000502:physiology; D013876:Thiophenes / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: C503102:1-(3-(2-(1-benzothiophen-5-yl) ethoxy) propyl)-3-azetidinol maleate; D016229:Amyloid beta-Peptides; D008298:Maleates; D018696:Neuroprotective Agents; D013876:Thiophenes
keywords: Alzheimer's disease; LTD; LTP; Oligomeric amyloid-β; Photo-cross-linked oligomeric amyloid-β; Synaptic plasticity; T-817MA; fEPSP